Prenatal exposure to antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model

Singer, Harvey S.; Morris, Christina; Gause, Colin; Pollard, Matthew; Zimmerman, Andrew W.; Pletnikov, Mikhail

doi:10.1016/j.jneuroim.2009.03.011

« Previous Next »Journal of Neuroimmunology
Volume 211, Issue 1 , Pages 39-48, 25 June 2009

Prenatal exposure to antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model

Harvey S. Singer
- Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Corresponding author. Johns Hopkins Hospital, Rubenstein Child Health Building, 200 N. Wolfe Street, Suite 2158, Baltimore, MD 21287, United States. Tel.: +1 410 955 7212; fax: +1 410 614 2297.
Christina Morris
- Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Colin Gause
- Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Matthew Pollard
- Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Andrew W. Zimmerman
- Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Kennedy Krieger Institute, Baltimore, MD, United States
Mikhail Pletnikov
- Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Received 13 November 2008; received in revised form 9 March 2009; accepted 9 March 2009. published online 13 April 2009.

Abstract

A pregnant mouse model was used to compare the effect of IgG, administered E13-E18, from mothers of children with autistic disorder (MCAD), to controls (simple- and IgG-) on behavioral testing in offspring. Mice, exposed in-utero to MCAD-IgG, as adolescents, were more active during the first ten minutes of central field novelty testing and, as adults, displayed anxiety-like behavior on a component of the elevated plus maze and had a greater magnitude of startle following acoustic stimulation. On a social interaction paradigm, adult mice had alterations of sociability. Pilot studies of immune markers in MCAD IgG-exposed embryonic brains suggest evidence of cytokine and glial activation. These studies demonstrate that the transplacental passage of IgG from MCAD is capable of inducing long-term behavioral consequences.

Keywords: Autism, Immune disorder, Neurobehavioral problems, Pregnant dam model, Transplacental antibodies